title: Dose-dependent effect of diaspirin cross-linked hemoglobin on regional blood circulation of severely hemorrhaged rats.
abstract: Diaspirin cross-linked hemoglobin (DCLHb), a hemoglobin-based blood substitute, has been found to improve systemic hemodynamics, cutaneous oxygen tension, and normalization of blood lactate levels and acid-base equilibrium after hemorrhage in animals. The present study was conducted to determine the dose-dependent effect of a 10% solution of DCLHb (20, 50, and 100% of shed blood volume; SBV) on regional blood circulation in hemorrhaged rats. Hemorrhage was induced in urethane-anesthetized rats by bleeding them at a rate of approximately .5 to 1 mL/min until a mean arterial pressure of 35-40 mmHg was achieved. This was maintained for up to 90 min to reach a base deficit of more than -12 mmol/L. Hemorrhage significantly decreased oxygen consumption, mean arterial pressure, cardiac output, stroke volume, and regional blood circulation, but increased total peripheral resistance. The vehicle Ringer's lactate (RL at 20% of SBV, intravenously) did not produce any improvements in oxygen consumption, base deficit, systemic hemodynamics, and regional blood circulation. DCLHb increased oxygen consumption, decreased base deficit, and produced significant improvements in systemic hemodynamics and regional blood flow in a dose-dependent manner. The increase in blood flow was highly significant until 60 min, but was less marked at 120 min, after resuscitation with DCLHb. Resuscitation with RL (300% of SBV) significantly improved systemic and regional blood circulation. However, the improvement was greater after resuscitation with DCLHb (50 or 100% of SBV) as compared with RL at 300% SBV. DCLHb in the dose of 50% of SBV produced maximal resuscitative effects, which were comparable to a DCLHb dose of 100% of SBV. The effect of DCLHb at 50% of SBV on renal cortical blood perfusion, concentration of moving red blood cells (CMBC), and blood velocity was also studied using laser Doppler flowmetry. Hemorrhage produced a decrease in renal cortical blood perfusion (85.3%), which was due to a decrease in the CMBC (61.0%) and their velocity (64.2%). Resuscitation with the RL did not produce any improvement in renal cortical perfusion. However, resuscitation with DCLHb significantly increased renal cortical perfusion (364.7%) due to an increase in both CMBC (123.4%) and their velocity (109.9%). It is concluded that DCLHb in a dose of 50% of SBV produces maximal improvement in regional blood circulation of hemorrhaged rats.
authors.affiliation: Department of Pharmaceutics & Pharmacodynamics, The University of Illinois at Chicago, Health Sciences Center 60612, USA.
authors.forename: A
authors.initials: A
authors.lastname: Gulati
authors.forename: A P
authors.initials: AP
authors.lastname: Sen
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects; D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001802:Blood Substitutes / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006439:Hemodynamics / Q000187:drug effects; D006454:Hemoglobins / Q000627:therapeutic use*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D012771:Shock, Hemorrhagic / Q000188:drug therapy*
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; C083478:diaspirin-cross-linked hemoglobin; D001241:Aspirin